Parathyroidectomy prior to kidney transplant decreases graft failure.

BACKGROUND: Uncorrected uremic hyperparathyroidism is associated with delayed graft function after kidney transplantation. The current guidelines of the Kidney Disease Improving Global Outcomes recommend maintaining parathyroid hormone ≤9x normal in patients pre-kidney transplantation. This study explores the effect of increased levels of serum parathyroid hormone and preoperative parathyroidectomy on outcomes after kidney transplantation. METHODS: A retrospective review was performed of adult patients who underwent kidney transplantation between January 1, 2005, and December 31, 2014, at a single institution. Biochemistries and outcomes were analyzed pre-kidney transplantation and at 30 days, 6 months, and 1 year post-kidney transplantation. RESULTS: A total of 913 patients underwent kidney transplantation from 2005-2014. Graft survival 1 year post-kidney transplantation was 97.8%. Overall, 462 (50.6%) patients had a pre-kidney transplantation diagnosis of uncorrected uremic hyperparathyroidism, which was associated with complications in the first year post-kidney transplantation (odds ratio 1.44; 95% confidence interval, 1.11-1.87); no statistical association with delayed graft function or graft failure was detected. Pre-kidney transplantation parathyroid hormone ≥6x normal was associated with post-kidney transplantation graft failure (P < .05). A total of 57 (6.2%) patients underwent pre-kidney transplantation parathyroidectomy, which was associated with lesser risk of graft failure (odds ratio: 0.547; 95% confidence interval, 0.327-0.913), but no statistically significant association with delayed graft function or complications were detected. CONCLUSION: Pre-kidney transplantation parathyroidectomy decreases post-kidney transplantation graft failure and may benefit patients whose serum parathyroid hormone levels decrease into the target range of current Kidney Disease Improving Global Outcomes guidelines.

Central venous parathyroid hormone monitoring using a novel, specific anatomic method accurately predicts cure during minimally invasive parathyroidectomy.

BACKGROUND: Measurement of intraoperative parathyroid hormone (PTH) levels is an important adjunct to confirm biochemical cure during parathyroidectomy. The purpose of this study was to evaluate a simplified anatomic technique for PTH sampling from the central veins through the minimally invasive neck incision, and to compare the predictive accuracy of central and peripheral PTH values. METHODS: A specific anatomic method for central PTH sampling was employed in 48 patients. Samples were drawn simultaneously from peripheral and central veins at baseline and 10 minutes postexcision of all hyperfunctioning parathyroid glands. RESULTS: The central venous PTH levels independently predicted biochemical cure according to the Miami criterion in all the patients. There was no significant difference in the postexcision central and peripheral values, which were 24.40 + 1.86 and 21.69 + 1.74, respectively (P = .877, ANOVA test). CONCLUSIONS: This study provides the original description of a simplified technique for measurement of intraoperative PTH levels in the central veins with direct comparison to peripheral venous levels, and confirmation of accuracy in predicting biochemical cure when relying on centrally obtained values alone.

Shifting patterns of genomic variation in the somatic evolution of papillary thyroid carcinoma.

BACKGROUND: Cancer is increasingly understood to arise in the context of dynamically evolving genomes with continuously generated variants subject to selective pressures. Diverse mutations have been identified in papillary thyroid carcinoma (PTC), but unifying theories underlying genomic change are lacking. Applying a framework of somatic evolution, we sought to broaden understanding of the PTC genome through identification of global trends that help explain risk of tumorigenesis. METHODS: Exome sequencing was performed on 53 PTC and matched adjacent non-tumor thyroid tissues (ANT). Single nucleotide substitution (SNS) signatures from each sample pair were divided into three subsets based on their presence in tumor, non-tumor thyroid, or both. Nine matched blood samples were sequenced and SNS signatures intersected with these three subsets. The intersected genomic signatures were used to define branch-points in the evolution of the tumor genome, distinguishing variants present in the tissues' common ancestor cells from those unique to each tissue type and therefore acquired after genomic divergence of the tumor, non-tumor, and blood samples. RESULTS: Single nucleotide substitutions shared by the tumor and the non-tumor thyroid were dominated by C-to-T transitions, whereas those unique to either tissue type were enriched for C-to-A transversions encoding non-synonymous, predicted-deleterious variants. On average, SNSs of matched blood samples were 81 % identical to those shared by tumor and non-tumor thyroid, but only 12.5 % identical to those unique to either tissue. Older age and BRAF mutation were associated with increased SNS burden. CONCLUSIONS: The current study demonstrates novel patterns of genomic change in PTC, supporting a theory of somatic evolution in which the zygote's germline genome undergoes continuous remodeling to produce progressively differentiated, tissue-specific signatures. Late somatic events in thyroid tissue demonstrate shifted mutational spectra compared to earlier polymorphisms. These late events are enriched for predicted-deleterious variants, suggesting a mechanism of genomic instability in PTC tumorigenesis.

Dissection of Levels II Through V Is Required for Optimal Outcomes in Patients with Lateral Neck Lymph Node Metastasis from Papillary Thyroid Carcinoma.

BACKGROUND: Completeness of surgical resection is an important determinant of outcomes in patients with papillary thyroid carcinoma and regional lymph node metastasis. The extent of therapeutic lateral neck dissection remains controversial. This study aims to assess the impact of modified radical neck dissection of levels II to V in a large patient series. STUDY DESIGN: Retrospective analysis of consecutive patients with papillary thyroid carcinoma who underwent lateral neck dissection at a single institution from June 1, 2006 to December 31, 2014 was performed. RESULTS: A total of 241 lateral neck dissections were performed in 191 patients (118 [62%] women; median age 46 years [range 6 to 87 years]; median follow-up 14.3 months [range 0.1 to 107 months]). Overall, 202 initial neck dissections (195 modified radical neck dissections and 7 less extensive dissections) were performed. Among these initial dissections, 137 (68.8%), 132 (65.7%), 105 (52.0%), and 33 (16.9%) had positive lymph nodes in levels II, III, IV, and V, respectively. Ipsilateral lymph node persistence or recurrence occurred after 22 (10.9%) initial dissections, at level II in 10 (45.5%), level III in 8 (36.4%), level IV in 7 (31.8%), and level V in 3 (13.6%). Thirty-nine reoperative lateral neck dissection were performed, including 18 cases of persistence and recurrence after our initial dissections. In reoperative dissections, positive lymph nodes were confirmed in levels II, III, IV, and V in 18 (46.2%), 10 (25.6%), 13 (33.3%), and 5 (12.8%) dissections, respectively. Temporary nerve injury occurred in 6 (3.0%) initial and 4 (10.3%) reoperative dissections, respectively. There were no permanent nerve injuries. CONCLUSIONS: Omitting levels II and V during lateral neck dissection for papillary thyroid carcinoma potentially misses level II disease in two-thirds of patients and level V disease in one-fifth of patients. Formal modified radical neck dissection is necessary to avoid the morbidity of reoperative surgery.

Real-Time Super Selective Venous Sampling in Remedial Parathyroid Surgery.

BACKGROUND: Remedial cervical exploration for persistent or recurrent primary hyperparathyroidism can be technically difficult, but is expedited by accurate preoperative localization. We investigated the use of real-time super selective venous sampling (sSVS) in the setting of negative noninvasive imaging modalities. STUDY DESIGN: We performed a retrospective analysis of a prospective database incorporating real-time sSVS in a tertiary academic medical center. Between September 2001 and April 2014, 3,643 patients were referred for surgical treatment of primary hyperparathyroidism. Of these, 31 represented remedial patients who had undergone one (n=28) or more (n=3) earlier cervical explorations and had noninformative, noninvasive preoperative localization studies. RESULTS: We extended the use of the rapid parathyroid hormone assay in the interventional radiology suite, generating near real-time data facilitating onsite venous localization by a dedicated interventional radiologist. The predictive value of real-time sSVS localization was investigated. Overall, sSVS correctly predicted the localization of the affected gland in 89% of cases. Of 31 patients who underwent sSVS, a significant rapid parathyroid hormone gradient was identified in 28 (90%), localizing specific venous drainage of a culprit gland. All patients underwent subsequent surgery and were biochemically cured, with the exception of one who had metastatic parathyroid carcinoma. Three patients with negative sSVS were also explored and cured. CONCLUSIONS: Preoperative parathyroid localization is of paramount importance in remedial cervical explorations. Real-time sSVS is a sensitive localization technique for patients with persistent or recurrent primary hyperparathyroidism, when traditional noninvasive imaging studies fail. These results validate the utility and benefit of real-time sSVS in guiding remedial parathyroid surgery.

Modern experience with aggressive parathyroid tumors in a high-volume New England referral center.

BACKGROUND: Parathyroid carcinoma (PTCA) is an exceptionally rare malignancy, often with a clinical presentation similar to that of benign atypical parathyroid adenoma. Its low incidence portends unclear guidelines for management. Accordingly, thorough examination of clinical and pathologic variables was undertaken to distinguish between PTCA and atypical adenomas. STUDY DESIGN: This was a retrospective analysis of a prospective database at a tertiary academic referral center. Between September 2001 and April 2014, 3,643 patients were referred for surgical treatment of PHPT. Of these, 52 harbored aggressive parathyroid tumors: parathyroid carcinomas (n=18) and atypical adenomas (n=34). We analyzed the surgical and clinicopathologic tumor characteristics, and did a statistical analysis. We measured preoperative and intraoperative variables, and postoperative and pathologic outcomes. RESULTS: Parathyroid carcinoma patients present with significantly increased tumor size (3.5 cm vs 2.4 cm, respectively; p=0.002), mean serum calcium (13.0 vs 11.8 mg/dL, respectively; p=0.003) and intact parathyroid hormone (iPTH) levels (489 vs 266 pg/mL, respectively; p=0.04), and a higher incidence of hypercalcemic crisis, compared with patients with atypical adenomas (50% vs 19%, respectively; p=0.072). Parathyroid carcinoma more frequently lacks a distinct capsule (47.1% vs 12.9%, respectively; p=0.03) and adheres to adjacent structures (77.8% vs 20.6%, respectively; p=0.017). Of note, there was no significant difference in loss of parafibromin expression between groups. CONCLUSIONS: Clinical distinction between PTCA and atypical adenomas is of critical importance in determining the appropriate extent of resection and follow-up. Loss of parafibromin has not been shown to distinguish between PTCA and atypical adenoma; clearer definition of clinicopathologic criteria for PTCA is warranted and may lead to improved postoperative management.

Heart block and acute kidney injury due to hyperparathyroidism-induced hypercalcemic crisis.

We describe a patient who presented with multi-system organ failure due to extreme hypercalcemia (serum calcium 19.8 mg/dL), resulting from primary hyperparathyroidism. He was found to have a 4.8 cm solitary atypical parathyroid adenoma. His course was complicated by complete heart block, acute kidney injury, and significant neurocognitive disturbances. Relevant literature was reviewed and discussed. Hyperparathyroidism-induced hypercalcemic crisis (HIHC) is a rare presentation of primary hyperparathyroidism and only a small minority of these patients develop significant cardiac and renal complications. In cases of HIHC, a multidisciplinary effort can facilitate rapid treatment of life-threatening hypercalcemia and definitive treatment by surgical resection. As such, temporary transvenous cardiac pacing and renal replacement therapy can provide a life-saving bridge to definitive parathyroidectomy in cases of HIHC.

A randomized, prospective trial of operative treatments for hyperparathyroidism in patients with multiple endocrine neoplasia type 1.

BACKGROUND: Hyperparathyroidism (HPT) in multiple endocrine neoplasia (MEN) type 1 is associated with multiglandular parathyroid disease. Previous retrospective studies comparing subtotal parathyroidectomy (SP) and total parathyroidectomy with autotransplantation (TP/AT) have not established clearly better outcomes with either procedure. METHODS: Patients were assigned randomly to either SP or TP/AT and data were collected prospectively. The rates of persistent HPT, recurrent HPT, and postoperative hypoparathyroidism were compared. RESULTS: The study cohort included 32 patients randomized to receive either SP or TP/AT (mean follow-up, 7.5 ± 5.7 years). The overall rate of recurrent HPT was 19% (6/32). Recurrent HPT occurred in 4 of 17 patients (24%) treated with SP and 2 of 15 patients (13%) treated with TP/AT (P = .66). Permanent hypoparathyroidism occurred in 3 of 32 patients (9%) overall. The rate of permanent hypoparathyroidism was 12% in the SP group (2/17) and 7% in the TP/AT group (1/15). A second operation was performed in 4 of 17 patients initially treated with SP (24%), compared with 1 of 15 patients undergoing TP/AT (7%; P = .34). CONCLUSION: This randomized trial of SP and TP/AT in patients with MEN 1 failed to show any difference in outcomes when comparing results of SP versus TP/AT. Both procedures are associated with acceptable results, but SP may have advantages in that is involves only 1 surgical incision and avoids an obligate period of transient postoperative hypoparathyroidism.

Minimally invasive, nonendoscopic thyroidectomy: a cosmetic alternative to robotic-assisted thyroidectomy.

BACKGROUND: The desire to improve cosmesis has driven the introduction of robotic-assisted and video-assisted thyroidectomy techniques. We report on minimally invasive thyroidectomy (MIT) through a 2-cm incision without the added need for video assistance and hypothesize similar clinical results to standard open thyroidectomy. METHODS: Between May 2012 and December 2013, 62 nonendoscopic MIT were evaluated for demographics, clinical outcomes, and patient satisfaction on a 1-10 scale. The results were compared with a case-matched control group who underwent conventional open thyroidectomy by the same surgeon. RESULTS: The 124 study patients demonstrated no differences between groups for demographics or clinical outcomes except a smaller thyroid lobe in the MIT group (9.2 vs 11.7 g; P = .05). There were longer operative times in the MIT group (135.4 vs 119.6 minutes; P = .07) that were not equivalent by equivalence testing (P = .534). In MIT patients, transient recurrent laryngeal nerve injury occurred per nerves at risk (1.1% vs 3.4%; P = .62) with no permanent injuries in either group. There was no difference in symptomatic hypocalcemia (9.7% vs 11.3%; P = .77) and postoperative hematoma (0% vs 3.2%; P = .50). On follow-up, the measured MIT scar was significantly shorter (2.22 vs 3.98 cm; P < .00001), which resulted in significantly improved cosmetic satisfaction ratings (9.56 vs 8.66; P = .03). CONCLUSION: In selected patients, MIT through a 2-cm incision without endoscopic assistance is a safe alternative to standard open thyroidectomy in the hands of an experienced endocrine surgeon. The operating time is slightly increased, but clinical results are equivalent and patient satisfaction is significantly improved.